tbuckley/cabot-search huggingface dataset:
Real-world outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) in 2L+ in the United States (US).
Authors: Kevin Kalinsky, Laura Spring, Clinton Yam, Aliki Taylor, Nikoleta Sjekloca, Alpana Kaushiva, Catherine Lai, Ioanna Ntalla, Rita Nanda
Journal: Journal of Clinical Oncology (2023)

e18879 Background: Pts with mTNBC have poor prognosis and limited treatment options. SG is an anti—Trop-2 antibody-drug conjugate approved in multiple countries for pts with mTNBC who received at least 1 prior systemic therapy and in the US for pts with pretreated HR+/HER2- mBC. In the pivotal phase 3 ASCENT study (NCT02574455), SG demonstrated superior efficacy over single-agent chemotherapy and a manageable safety profile in pts with mTNBCardia A, et al. NEJM. 2021). This study is, to our knowledge, the first to describe real-world treatment patterns and dosing with SG and its impact on clinical outcomes in pts with mTNBC in the US. Methods: This retrospective, observational cohort study used the ConcertAI Patient360™ dataset with additional curated electronic medical record data from the US. Pts (≥18 years) diagnosed with mTNBC as defined according to the current American Society of Clinical Oncology/College of American Pathologists guidelines (HER2 IHC0, 1, or 2/ISH-negative; ER/PR &lt;1%) and initiating treatment with SG (index date) in 2L+ from April 2020 to May 2022 were included. Real-world clinical outcomes with SG and use patterns were assessed. Kaplan-Meier method was used to determine real-world overall survival (rwOS). Results: In total, 230 pts met the eligibility criteria and were included for analysis. All pts were female; 64% were White and 26% Black; median age was 60 years (IQR, 49-69); 71% of pts presented with ECOG performance status ≤1; 71% had visceral metastases and 7% had brain metastases at baseline. The median time from mBC diagnosis to SG treatment initiation was 11.8 months (IQR, 7.6-19.2). Most pts (66%) were treated in a community setting; 34%, 28%, 19%, and 20% of pts were treated with SG in the 2L, 3L, 4L, and 5L+ setting, respectively. Between 2020-2022, there was a trend in the distribution of SG use shifting to earlier line settings, see Table. Median starting dose was 10 mg/kg (IQR, 9.8-10.1). Median follow-up duration was 7.2 months (IQR, 3.9-11.1). Median rwOS (95% CI) from index date was 10 months (8.3-11.1) among all pts. Median rwOS (95% CI) was 13.9 months (9.79-not estimable) and 8.4 months (7.7-10.3) among pts treated with SG in 2L and in 3L+ setting, respectively. Analyses on real-world patterns of SG use are ongoing and additional results will be provided. Conclusions: Pts who were treated with SG in routine clinical practice were older, more ethnically diverse, and presented with worse performance status than pts enrolled in the ASCENT trial but demonstrated a similar survival benefit. The proportion of pts treated with 2L SG increased from 2020 to 2022, reflecting an expected dynamic of post approval drug uptake in routine practice. [Table: see text]
Preliminary results of a phase 1, first-in-human study of INA03, an anti-CD71 antibody-drug conjugate, in patients with relapsed or refractory (R/R) acute leukemias.
Authors: Sylvain Garciaz, Pierre Bories, Leonor Lopez Almeida, Jean-Marie Boher, Coralie Belanger, Christian Recher, Olivier Hermine, Norbert Vey, Pierre Launay
Journal: Journal of Clinical Oncology (2023)

7045 Background: R/R acute leukemias (AL) represent major therapeutic challenges. Several reports have highlighted the role of iron metabolism in various proliferative tumor models including AL including the over-expression of the transferrin receptor (TfR1/CD71). Our strategy is thus to harness CD71 overexpression to specifically target cytotoxic agents to leukemic cells. INA03 is an antibody drug conjugate (ADC) constituted of a humanized monoclonal IgG 4 against CD71 and the microtubule disrupting agent monomethyl auristatin E (MMAE). We herein report the preliminary safety and efficacy data of INA03 from a phase 1/2 trial in patients (pts) with R/R AL (NCT03957915). Methods: INA03 is given as 30 minutes IV infusion on days 1 (Loading dose (LD)) followed by maintenance injections on D15 for cycle 1 and on D1 and D15 of cycle 2 and beyond. Eligibility criteria are: R/R AL after at least one line of treatment including high dose chemotherapy and/or Vidaza and Venetoclax, AlloSCT &gt; 18y, with FEVG &gt; 50%, Creatinine Clearance &gt; 30ml/min, normal liver function, ECOG &lt; 2. The study design is based on a continuous reassessment method and includes 2 parts: a LD Titration study (Part 1, completed), followed by a Dose Escalation Part 2. During Part 1, sequential cohorts of 2 pts were included to receive ascending LD of INA03 followed by subsequent fixed dose of INA03 to deal with a potential sink effect related to the high expression of CD71 in normal erythroblasts. During Part 2, sequential cohorts of 3 pts received escalating doses of INA03 Q2 weeks in 28-day cycles. The objectives were to establish the MTD for subsequent administration and both safety/tolerability and anti-leukemic activity. Results: With a cutoff date of January 18, 2023, 22 pts across 8 cohorts were included in the study. The median age was 73 (range: 39 – 83), 20 (91%) pts had AML and two (9%) had ALL. Three (13.6%) pts had a prior allo-SCT and 12 (54.5%) had prior VEN exposure. Pts received escalating doses of INA03 of 0.02 mg/kg to 2 mg/kg. MMAE pharmacokinetics (PK) appears dose-proportional with a small accumulation after repeated IV, while INA03 PK exhibits target-mediated drug disposition without accumulation. No DLT was observed among the 18 DLT-evaluable pts, up to the highest dose of 2 mg/kg. No grade 2-4 TEAEs were observed. One related grade 1 TEAE (hyperkalemia/phosphatemia) was reported. Transient decrease of reticulocyte count and erythroblasts percentage were observed at 0.5 mg/kg and above. Blasts reductions were seen in 3/18 evaluable pts at dose &gt; 1 mg/kg including two partial responses. Conclusions: INA03 is well tolerated up to the dose of 2 mg/kg with some efficacy signals in R/R AL. The trial continues to accrue patients. Clinical trial information: NCT03957915 .
Utility of a novel trainee-level hematology/oncology podcast in graduate medical education.
Authors: Ronak Mistry, Vivek Patel, Daniel Hausrath
Journal: Journal of Clinical Oncology (2023)

11027 Background: Despite the popularity of podcasts in medical education, there are a limited number of trainee-level hematology/oncology (H/O) podcasts. We created &amp; implemented a novel H/O podcast curriculum to address this barrier. Here, we evaluated the utility of this podcast for H/O fellows &amp; internal medicine (IM) residents on H/O rotations. Methods: We included IM residents &amp; H/O fellows at Vanderbilt University Medical Center in the 2022-2023 academic year. Each IM resident starting on a H/O inpatient rotation received an email prior to their rotation with list of recommended episodes. H/O fellows were encouraged to listen to episodes at their discretion. We developed anonymous surveys using a 5-point Likert scale (1, “strongly disagree” to 5, “strongly agree”) to understand how the podcast helped prepare them clinically &amp; if H/O podcasts were effective educational tools. Results: A total of 20 trainees completed the survey including 7 residents (35%) &amp; 13 fellows (65%). All post-graduate years were represented. Results of the survey are presented in the table. Most felt the podcast material helped with inpatient rotations &amp; consults, was clinically relevant, &amp; helped with clinical decision-making with a mean score of 4.76, 4.79, and 4.50, respectively. Respondents agreed the fundamentals of H/O are amenable to a podcast platform &amp; are likely to continue to use podcasts as learning tools in H/O with a mean score of 4.68 and 4.40, respectively. When restricting to the fellow cohort, the majority felt that the podcast material helped them prepare for their clinic patients with a mean score of 4.62. Most found the podcast convenient &amp; the most common activities while listing to our podcast were driving (70%), doing chores (35%), exercising (25%), and eating (25%). Conclusions: H/O fellows &amp; IM residents found the trainee-level podcast curriculum clinically relevant and helped with clinical decision making. The respondents also all agreed or strongly agreed that podcasts are an effective medium to teach hematology/oncology. Our successfully piloted podcast curriculum can be adapted to other training programs to improve foundational knowledge in oncology. [Table: see text]
The SMILE scale: A pilot study among patients with cancer.
Authors: Laura Vater, Ali Ajrouch, Patrick O. Monahan, Laura Jennewein, Yan Han, Ahmad Karkash, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2023)

e24036 Background: In the US, it is projected that more than 22 million people will be living with cancer by 2030. As survivorship increases, there is a need for simple, convenient tools to quantify patient quality of life and encourage healthy behaviors. To fill this gap, a new psychometric tool named the SMILE Scale was created. The SMILE Scale is a brief self-administered questionnaire assessing the frequency of behaviors intended to improve wellness in five domains: Sleep, physical activity (Move), stress management (Inhale and Exhale), social interactions (Love and connect), and nutrition (Eat to nourish). In this study, we aimed to determine the feasibility of collecting daily self-reported SMILE Scale data and weekly quality of life data, via electronic surveys in patients with cancer. We also aimed to measure the association between SMILE Scale responses and validated health-related quality of life (HRQOL) tools (PROMIS-29+2 and SymTrak-8) as a pilot test of the hypothesis that increased wellness behaviors may impact quality of life. Methods: We surveyed 100 patients with cancer at the IU Simon Comprehensive Cancer Center. Participants were asked to complete daily SMILE Scale assessments over a two-week period, as well as weekly PROMIS-29+2 and SymTrak-8 surveys. The primary endpoint was the SMILE Scale completion rate. Secondary endpoints in this single-arm pilot study included correlations between SMILE Scale results and the other HRQOL tools. Results: Daily completion rate of the SMILE Scale ranged from 57% to 65% of participants over a 14-day period. Among the 61% of participants who completed SMILE on day 1, 87% completed SMILE on 10 of 14 days. Further, 77% completed SMILE at least 1 of the 14 days. By end of study, participants who self-reported more wellness behaviors (i.e., higher daily SMILE scores) demonstrated significantly higher PROMIS physical health (p = .003), higher PROMIS mental health (p = .008), and lower (better) SymTrak total symptom burden (p = .006). Further, among those who completed at least 1 of 14 daily SMILE assessments, quality of life significantly improved over the two-week period for PROMIS mental health (p = .018) and SymTrak total symptom burden (p = .014). Conclusions: The SMILE Scale completion rate on any given day did not satisfy our pre-planned ≥70% threshold for feasibility; however, the rate for completing SMILE at least once during the 14 days (77%) met this threshold. There is growing recognition that interventions with modest uptake may benefit interested patients. The SMILE completion rate across 14 days among those who completed at least one day indicates benefit for providing a daily or on-demand option for those interested. Further, significant correlative results between SMILE scores and secondary QOL endpoints suggest a potential benefit for delivering SMILE in clinical practice and warrants testing the SMILE Scale’s causal impact in a future randomized trial.
Radiation-induced nasopharyngeal necrosis in locally-recurrent nasopharyngeal carcinoma patients after re-radiotherapy.
Authors: Runda Huang, Jingjing Miao, Lu Zhang, Yinglin Peng, Shaomin Huang, Fei Han, Lin Wang, Xiao-Wu Deng, Chong Zhao
Journal: Journal of Clinical Oncology (2023)

e18063 Background: Re-radiotherapy (re-RT) is the main treatment for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and commonly led to radiation-induced nasopharyngeal (NP) necrosis, which was lethal but rare study has focused on it. The aim of this study was to evaluate the cause and impact of radiation-induced NP necrosis in lrNPC patients who received re-RT. Methods: Totally 252 lrNPC patients who received re-RT between January 2013 and December 2020 were retrospectively collected. The inclusion criteria were as follows: (1) no NP necrosis before re-RT; (2) complete medical records, including treatment, clinical and dosimetric information; (3) conventional fractionated radiotherapy. All patients received intensity-modulated radiotherapy ± chemotherapy. Radiation-induced NP necrosis was diagnosed by magnetic resonance imaging and/or electronic nasopharyngoscopy. Dosimetric factors of the planning target volume of primary tumor (PTVp) were extracted from the dose-volume histogram (DVH), which was rescaled to an equivalent dose of 2 Gy per fraction (EQD 2 Gy) using a linear quadratic model. Logistic regression was used to identify the independent prognostic factors for generating the nomogram. Results: With a median follow-up of 44.63 months (inter-quartile range [IQR], 27.70 – 69.20 months), 47.6% of patients (120/252) occurred radiation-induced NP necrosis, which mostly happened within 1 year post re-RT (median [IQR], 5.83 [3.37 – 11.57] months). The 3-year overall survival was 83.0% vs 39.7% ( P＜0.001) in lrNPC patients with or without radiation-induced NP necrosis. Except for the fractionated dose, other dosimetric factors of PTVp were not significantly different between two groups, including D 98 (dose to 98% of PTVp), D 50 , D 2 and homogeneity index (Table). Furthermore, multivariate analysis showed that continuous variable age (HR [95%CI]: 1.04 [1.02 – 1.07], P = 0.003) and tumor volume (HR [95%CI]: 1.02 [1.01 – 1.03], P＜0.001), and fractionated dose &gt; 2.22 Gy (HR [95%CI]: 2.36 [1.32 – 4.21], P = 0.004) were independent factors in predicting radiation-induced NP necrosis, which yielded a C-index of 0.742 (95% CI, 0.682 - 0.803) for OS in the nomogram. Conclusions: The incidence of radiation-induced NP necrosis was high in lrNPC patients who received re-RT. Patients with older age, larger tumor volume or receiving fractionated dose over 2.22 Gy were more easily to suffer NP necrosis, which need to explore novel treatment strategies to improve patients’ survivals. [Table: see text]
Metastases harbored in the maxillofacial region: Patient and cancer related characteristics and outcomes.
Authors: Shahar Turgeman, Ilit Turgeman, Omri Emodi, Amir Wolff, Adi Rachmiel
Journal: Journal of Clinical Oncology (2023)

e18029 Background: Maxillofacial metastases from distal primary sites are rare, accounting for less than 1% of all newly diagnosed cancer in the head and neck region. Clinical manifestation is non-specific and lesions are often misdiagnosed as benign or inflammatory lesions, and mistreated. We sought to describe maxillofacial metastases and evaluate associations with treatment and patient related outcomes. Methods: Data from all patients diagnosed with cancer in the maxillofacial region between 2008-2020 were extracted retrospectively from the hospital registry, and those with radiological and histological evidence of metastatic lesions were included in the analysis. Patient demographics, clinical presentation, features of primary cancer and treatment were collected. Paired t-tests and univariate regression models were used to evaluate an association between variables and overall survival (OS). Results: Of 532 patients diagnosed with cancer in the maxillofacial region, 15 (2.8%) were found to have metastases from distal primary cancers and included in the study. The group comprised 8 males (53.3%) and 7 females (46.6%), mean age 69 years (range 43 -88) and most common primary malignancies were lung (27%), gastrointestinal (27%) and prostate (20%), with 60% adenocarcinoma histology and the rest SCC and undifferentiated carcinoma. Presenting symptoms included trismus, pain, and swelling in 40% of cases. Clinically, most intraoral manifestations were classic oral ulcerations while the most frequent extra oral features were diffuse pre-auricular and mandibular swelling. Mean time to diagnosis was 22 days (range 7-60), however, intraoral lesions were diagnosed numerically earlier than extra oral (18 vs 23 days, p = 0.5). The mandible was the primarily involved hard tissue location (40%), and the parotid, for soft tissue lesions (33%). Mean SUV for PET-CT scans was 4.4 (range 2.0-10.93) and CT demonstrated bone expansion and lysis (50% each) and periosteal reaction (33%). In total, 60% of patients in the study had a change to their treatment after diagnosing the metastasis, while 40% with direct radiation (30-70 Gy) to the metastatic site. Median OS was 5 months while 60% of patients in the study group survived less than 6 months. Despite being twice as likely to receive treatment (75% vs 37.5%), patients with intra oral metastases had significantly shorter survival than those with extra oral metastases (13.3 vs 2.9 months, 95% CI 3.025-17.689, p &lt; 0.01). No other associations were observed between patient demographics, cancer type and treatment, with survival. Conclusions: The maxillofacial region appears to be a late site for cancer metastasis, with non-specific presentation. As patient survival outcomes improve across cancer types and the array of possible alternative diagnoses increases, clinicians should be aware of this entity to ensure rapid referral for diagnosis and palliative treatment.
Comprehensive geriatric assessment based multidisciplinary team intervention for hospitalized frail patients in oncology: COMPASS-ONCO/KCSG AL21-13.
Authors: Yun-Gyoo Lee, In Gyu Hwang, Su-Jin Koh, Soojung Hong, Jin Won Kim, Jee Hyun Kim
Journal: Journal of Clinical Oncology (2023)

TPS12138 Background: Comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary assessment for evaluating older patients’ medical, psychological, physical functions and social status. CGA-based multidimensional intervention is the gold standard in geriatric oncology to identify patients at high risk of adverse outcomes and optimize cancer and overall management. Numerous studies have demonstrated that CGA could modify oncologic treatment decision. However, little is known about the treatment outcomes of a multidisciplinary team intervention based on CGA. Methods: The COMPASS study is the first pragmatic multicentre trial within a cohort comprising three randomized controlled trials focusing on focusing on CGA and multidisciplinary intervention for hospitalised elderly patients in various healthcare settings of Korea. COMPASS-ONCO compares the effect of an oncologist-led multidisciplinary team intervention based on the CGA to that of conventional treatment for older cancer patients without the involvement of geriatricians. The patients will be randomised into the intervention or control groups in a 1:1 ratio. The inclusion criteria are as follows: (1) 65 years of age or older, (2) prefrail or frail status assessed by Korean version of the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight scale questionnaire, (3) having two or more of the following diseases; hypertension, diabetes, ischaemic heart disease, chronic lung disease, arthritis, stroke, depression, chronic kidney disease and dementia. (4) living at home for more than 3 months before hospitalization, (5) subject to palliative chemotherapy and (6) histologically confirmed gastric, colorectal, lung, pancreatic or biliary tract carcinoma. The intervention includes CGA and CGA-based multidisciplinary interventions by oncologists, nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is overall treatment utility which is a clinical outcome incorporating objective and subjective measures of anticancer efficacy, tolerability and acceptability. Additionally, recognition of advance directives, changes in body composition and validity of anticancer drug toxicity prediction model will also be assessed. Approximately 1040 patients will be required for COMPASS study, and 260 will be enrolled in the COMPASS-ONCO substudy at five hospitals in Korea. Participants have been recruited from 2 November 2021, and recruitment will continue until December 2024. Clinical trial information: KCT0006270 .
Limited and uneven geriatric cancer drug trials worldwide.
Authors: Huang Hui-Yao, Ye Leng, Dandan Cui, Yuan Fang, Yu Tang, Ning Li
Journal: Journal of Clinical Oncology (2023)

e24017 Background: Conducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric cancer drug trials worldwide over the last decade. Methods: Up-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase. Results: 582 geriatric cancer drug trials were identified, with 292 trials for solid cancer while the other 290 trials were for hematological malignancies. Among them, 307 were single-region studies, 407 were initiated by academic groups, and 96 were terminated. Decreasing trends in the annual number of all trials (-3.8% per year) were observed over time, especially in solid tumor (-9.2% per year). For all these trials, 303 were conducted in Asia; this number was significantly higher than that in Europe (174), North America (129), Oceania (27) and South America (8). Similar difference was found in participation rate in trials by academic groups ranging from 59.5% in Asia to 0.5% in South America. In terms of development time, 86 and 176 were initiated before drug and indication approval, respectively, and the remaining 320 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (68.4%), while phase I trials accounted for the lowest proportion (7.2%). Compared with the hematological malignancies, trials on solid tumor had a higher terminated rate(18.8% vs 14.1%, p= 0.032) and were less likely to initiated before drug approval(6.5% vs. 23.1%, p&lt; 0.0001) . Treatment was explored for 21 different cancers, with leukaemia, lung cancer and lymphoma being the most common. Conclusions: Geriatric trials of cancer drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication. [Table: see text]